Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility,

The function of the sino-atrial node (SAN), the pacemaker of the heart, is known to decline with age, resulting in pacemaker disease in the elderly. The aim of the study was to investigate the effects of ageing on the SAN by characterizing electrophysiological changes and determining whether changes in gene expression are involved. In young and old rats, SAN function was characterized in the anaesthetized animal, isolated heart and isolated right atrium using ECG and action potential recordings; gene expression was characterized using quantitative PCR. The SAN function declined with age as follows: the intrinsic heart rate declined by 18 ± 3%; the corrected SAN recovery time increased by 43 ± 13%; and the SAN action potential duration increased by 11 ± 3% (at 75% repolarization). Gene expression in the SAN changed considerably with age, e.g. there was an age-dependent decrease in the Ca 2+ clock gene, RYR2, and changes in many ion channels (e.g. increases in Na v 1.5, Na v β1 and Ca v 1.2 and decreases in K v 1.5 and HCN1). In conclusion, with age, there are changes in the expression of ion channel and Ca 2+clock genes in the SAN, and the changes may provide a partial explanation for the age-dependent decline in pacemaker function.

Although both metoprolol and ivabradine comparably prevented post-MI deterioration of haemodynamic function in the rat, metoprolol had additional potentially beneficial effects; it prevented LV dilation and hypertrophy, chronotropic incompetence, strongly increased contractility of isolated cardiomyocytes, and prevented the potentially proarrhythmic increase in NCX activity. This indicates that pure HRR does not account for effects of beta-blockade in the post-MI setting. Metoprolol and ivabradine similarly improve LV function, although differently affect LV morphology and cellular Ca2+ handling in the post-infarction rat heart.

Chromophobe renal cell carcinoma (ChRCC) is a subtype of renal cell carcinoma (RCC). ChRCC is diagnosed mainly in 6th decade of life. An incidence of ChRCC is similar in both men and woman. Eighty six percent of ChRCCs cases are diagnosed in stage 1 or 2. Prognosis of ChRCC is better than in other types of RCC. Five- and 10-year disease free survival (DFS) for ChRCC was 83.9% and 77.9%, respectively. Expression of immunohistological markers: cytokeratins (CK), vimentin, epithelial membrane antigen (EMA), CD10 could be potentially helpful in diagnosis of different subtypes of RCC. From all conventional RCC, CD 117 was detected (overexpression) in membrane of cells ChRCC.Overexpression of CD117 on cellular membranes of ChRCC could be a potential target for kinase inhibitors like: imatinib, dasatinib, nilotinib. The potential targets for other kinase inhibitors (sunitinib and sorafenib) in ChRCC seem to be VEGFR and PDGFR. On the basis for formulating research hypotheses which should be verified by prospective studies.

Background-Heart failure (HF) causes a decline in the function of the pacemaker of the heart-the sinoatrial node (SAN).The aim of the study was to investigate HF-induced changes in the expression of the ion channels and related proteins underlying the pacemaker activity of the SAN. Methods and Results-HF was induced in rats by the ligation of the proximal left coronary artery. HF animals showed an increase in the left ventricular (LV) diastolic pressure (317%) and a decrease in the LV systolic pressure (19%) compared with sham-operated animals. They also showed SAN dysfunction wherein the intrinsic heart rate was reduced (16%) and the corrected SAN recovery time was increased (56%). Quantitative polymerase chain reaction was used to measure gene expression. Of the 91 genes studied during HF, 58% changed in the SAN, although only 1% changed in the atrial muscle. For example, there was an increase in the expression of ERG, K v LQT1, K ir 2.4, TASK1, TWIK1, TWIK2, calsequestrin 2, and the A1 adenosine receptor in the SAN that could explain the slowing of the intrinsic heart rate. In addition, there was an increase in Na